title: Ouabain-induced cochlear nerve degeneration: synaptic loss and plasticity in a mouse model of auditory neuropathy.
abstract: Ouabain application to the round window can selectively destroy type-I spiral ganglion cells, producing an animal model of auditory neuropathy. To assess the long-term effects of this deafferentation on synaptic organization in the organ of Corti and cochlear nucleus, and to ask whether surviving cochlear neurons show any post-injury plasticity in the adult, we quantified the peripheral and central synapses of type-I neurons at posttreatment times ranging from 1 to 3 months. Measures of normal DPOAEs and greatly reduced auditory brainstem responses (ABRs) confirmed the neuropathy phenotype. Counts of presynaptic ribbons and postsynaptic glutamate receptor patches in the inner hair cell area decreased with post-exposure time, as did counts of cochlear nerve terminals in the cochlear nucleus. Although these counts provided no evidence of new synapse formation via branching from surviving neurons, the regular appearance of ectopic neurons in the inner hair cell area suggested that neurite extension is not uncommon. Correlations between pathophysiology and histopathology showed that ABR thresholds are very insensitive to even massive neural degeneration, whereas the amplitude of ABR wave 1 is a better metric of synaptic degeneration.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Yuan
authors.forename: Fuxin
authors.initials: F
authors.lastname: Shi
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Yin
authors.forename: Mingjie
authors.initials: M
authors.lastname: Tong
authors.forename: Hainan
authors.initials: H
authors.lastname: Lang
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Polley
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
authors.forename: Albert S B
authors.initials: AS
authors.lastname: Edge
mesh_terms: D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D003056:Cochlear Nerve / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D051379:Mice; D008808:Mice, Inbred CBA; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects*; D009925:Organ of Corti / Q000473:pathology / Q000503:physiopathology; D010042:Ouabain / Q000009:adverse effects* / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000469:parasitology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D061285:Vestibulocochlear Nerve Injuries / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D017470:Receptors, Glutamate; D010042:Ouabain